1,3-Dibromo-5,5-dimethylhydantoin → 7-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 1099249Notes

Reaction equation

HRID 1099249 reaction equation
[N:1]1[N:2]2[CH:10]=[CH:9][CH:8]=[C:3]2[C:4]([NH2:7])=[N:5][CH:6]=1.[Br:11]N1C(C)(C)C(=O)N(Br)C1=O.CO.C(Cl)Cl.[O-]S([O-])=O.[Na+].[Na+]>CN(C=O)C.C(OCC)(=O)C>[Br:11][C:10]1[N:2]2[C:3]([C:4]([NH2:7])=[N:5][CH:6]=[N:1]2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 24437Sodium SulfiteHCID 10441749Pyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 21226129Dichloromethane methanol

Product 1

HCID 422813837-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amineYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

A stirred solution containing pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (21.0 g, 0.157 mol) in anhydrous DMF (200 mL) was cooled to −20° C. and 1,3-dibromo-5,5-dimethylhydantoin (22.4 g, 0.078 mol) was added portionwise over ˜45 minutes. The reaction was stirred for another 45 minutes and monitored for completion by TLC (silica gel, GHLF, 5% CH3OH/CH2Cl2). Saturated Na2SO3 solution (300 mL) was added, the resulting suspension was stirred and the solids were collected by suction filtration. The filter cake was washed with water, dried by suction and then partitioned between ethyl acetate (1L) and 5% sodium carbonate solution (1L). The layers were separated, the organic layer was washed with fresh sodium carbonate solution and dried over magnesium sulfate. The filtrate from the work-up was also extracted and combined with the main batch then filtered through a pad of Magnesol and concentrated in vacuo to afford crude mono-bromide, KRAM 206-3-1, 29.9 g, 90% yield. Trituration of a 21.5 g quantity of the crude mono-/di-bromo product in hot ethyl acetate (300 mL, 70° C.) provided colorless solids (12.3 g) containing only ˜2% of the di-brominated side-product. 1H-NMR (CD3OD): δ 7.84 (s, 1H), 6.95 (d, 1H, J=4.7 Hz), 6.71 (d, 1H, J=4.7 Hz), 4.89 (s, 3H, —NH2+H2O); MS: LC/MS (+esi), m/z=213.1 [M+H].

Workup

  1. stirringthe resulting suspension was stirred
  2. filtrationthe solids were collected by suction filtration
  3. washThe filter cake was washed with water
  4. customdried by suction
  5. custompartitioned between ethyl acetate (1L) and 5% sodium carbonate solution (1L)
  6. customThe layers were separated
  7. washthe organic layer was washed with fresh sodium carbonate solution
  8. dry with materialdried over magnesium sulfate
  9. extractionThe filtrate from the work-up was also extracted
  10. filtrationthen filtered through a pad of Magnesol
  11. concentrationconcentrated in vacuo
  12. customto afford crude mono-bromide, KRAM 206-3-1, 29.9 g, 90% yield

Sources & evidence

ORD record
ord-35a89b795e994e6dbb917f8e6fe8092b
Source dataset
uspto-grants-2012_03
Patent number
US08143393B2

Reaction notes

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